MicroRNA‐214 Is Upregulated in Heart Failure Patients and Suppresses XBP1‐Mediated Endothelial Cells Angiogenesis
| Autor: | Peihua Wang, Ming-Hui Zou, Feng Wang, Sandip Chaugai, Lei Yang, Wei Gong, Quanlu Duan, Chen Chen, Dao Wen Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
X-Box Binding Protein 1 medicine.medical_specialty XBP1 Physiology Angiogenesis Clinical Biochemistry Blotting Western Neovascularization Physiologic Regulatory Factor X Transcription Factors Biology Real-Time Polymerase Chain Reaction Mice Downregulation and upregulation Internal medicine Original Research Articles microRNA medicine Gene silencing Animals Humans Original Research Article Aged Tube formation Heart Failure Endothelial Cells Cell Biology Middle Aged medicine.disease Immunohistochemistry Up-Regulation DNA-Binding Proteins Mice Inbred C57BL MicroRNAs Endocrinology Gene Expression Regulation Heart failure Gene Knockdown Techniques Cancer research Ectopic expression Female Transcription Factors |
| Zdroj: | Journal of Cellular Physiology |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | More and more miRNAs have been shown to regulate gene expression in the heart and dysregulation of their expression has been linked to cardiovascular diseases including the miR-199a/214 cluster. However, the signature of circulating miR-214 expression and its possible roles during the development of heart failure has been less well studied. In this study, we elucidated the biological and clinical significance of miR-214 dysregulation in heart failure. Firstly, circulating miR-214 was measured by quantitative PCR, and we found that miR-214 was upregulated in the serum of chronic heart failure patients, as well as in hypertrophic and failing hearts of humans and mice. Adeno-associated virus serotype 9 (AAV9)-mediated miR-214 silencing attenuates isoproterenol (ISO) infusion-induced cardiac dysfunction and impairment of cardiac angiogenesis in mice. Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation, and reverses anti-angiogenic effect of miR-214 over expression. All these findings suggest that miR-214 is an important regulator of angiogenesis in heart in vitro and in vivo, likely via regulating the expression of XBP1, and demonstrate that miR-214 plays an essential role in the control/inhibition of cardiac angiogenesis. J. Cell. Physiol. 230: 1964–1973, 2015. © 2015 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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